Abstract
Background. Cyclosporine (CsA) is implicated in the development of chronic allograft nephropathy, which is related to reduced long-term allograft survival. The activation of tubular epithelial cells is involved in the renal scarring process via stimulation of factors such as endothelin-1 (ET-1) and nitric oxide (NO). The effect of CsA on the activation of tubular epithelial cells towards increased production of ET-1 and NO was investigated in this study. Methods. Human tubular epithelial cells (HK-2) were cultured in the presence of CsA at different concentrations (125, 250, 500, and 1,000 ng/mL). ET-1 m-RNA and NO production were measured using RT-PCR and Griess method, respectively. The cytotoxic effect of CsA was examined by the MTT method and cell count. Results. A statistically significant and dose-dependent cytotoxic effect of cyclosporine on HK-2 cells was observed. A dose-dependent up-regulation of ET-1 mRNA production and NO accumulation was observed under the influence of CsA. Conclusion. Increased synthesis of endothelin-1 mRNA and nitric oxide as well as a significant cytotoxic effect on tubular epithelial cells under the influence of CsA might be related to the development of CsA nephrotoxicity.
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